1.2.3- Triazoline ring

Nomenclature. The three forms of the 1,2,3-triazoline ring system along with their Chemical Abstracts naming are presented in Scheme 1. 

A 2-1,2,3-Triazoline ring from ethylene derivs. and azides... 

N-Condensed 1,2,3-triazoline ring by 1,3-dipolar cycloaddition Double ring closure... 

Figure 17.9 A general Huisgen reaction involves the cycloaddition of an azide with an alkene or an azide with an alkyne. The products of these reactions are a triazoline ring or a triazole ring, respectively.

Fluoroalkanesulfonyl azides 281 add readily to vinyl ethers to provide triazolines 282 in good yield (67-84%). At room temperature, slow decomposition of the products is observed with evolution of nitrogen and formation of piperazine derivatives 284. No other products are observed. Formation of piperazines 284 must involve cleavage of the triazoline ring with formation of zwitterionic intermediates 283 (Scheme 42) <2004JFC(125)445>. 

There are two main approaches to the synthesis of A2-l,2,3-triazolines these involve the union of the C—C and N—N—N fragments as in the olefin-azide additions or alternately building from the C—N and C—N—N moieties as achieved through the imine-diazoalkane reactions (Scheme 2). The choice is determined by the type of substitution desired on the triazoline ring. Imines in general can be more easily prepared than the corresponding olefins. 

The strained double bonds in Dewar benzene and thiophene make them good dipolarophiles in 1,3-cycloadditions. The hexamethyl,148 1,3,5-trimethyl, and perfluoro-1,3-dimethyl122 Dewar benzenes all yield a monoadduct by reaction with phenyl azide. The hexafluoro derivative, however, gives, depending on the conditions, either a monoadduct (19) or a mixture of mono-and bisadducts accompanied by an aziridine resulting from thermolysis of the triazoline ring system (Scheme 19).146... 

Reaction of aryl azide with cis-trans mixtures of enamines yields, under kinetically controlled conditions, only the trans-triazolines, as shown by NMR studies. At higher temperatures or in the presence of acid, however, the trans-triazoline epimerizes to give a cis-trans equilibrium mixture the isomer ratio at equilibrium is dictated by steric repulsions in the triazoline ring, and the size of the substituents does not seem to exert a significant effect.211 The proposed mechanism involves the breaking of the N-l/C-5 bond (Scheme 54), although an N-l/N-2 rupture is equally feasible. 

The polycondensation of 4,4 -diphenylene diazide with p-benzoquinone or ethylene dimethacrylate, leading to heat resistant oligomers containing triazoline and aziridine segments, also appears to proceed through the initial formation of triazoline rings, which later form aziridines.318... 

The reaction of 1-azidoadamantane with ethyl acrylate affords exclusively a 4-substituted triazoline.155 The assigned regiochemistry is supported by 1H-and 13C-NMR spectra. The H-NMR spectral characteristics of the triazoline ring protons are similar to those reported for the corresponding adduct from phenyl azide.32, 3C-NMR spectra reveal a characteristic triplet at 8 61.9 assignable to C-5. 55 Different NMR techniques have been used in structure assignments of isoindolo[2,l-c]-A2-triazolines,324 spiroanthrone-triazolines,193,194 5-heteroaryl-substituted A2-1,2,3-triazolines,329 and some l-fluoro-(5-trifluoromethyl)-A2-l,2,3-triazolines.356... 

For compound 63 the triazoline ring adopts an envelope conformation with C-5 at the flap of the envelope. The alkyl groups are equatorial, whereas the hydroxy group is axial. The interatomic distances and torsional angles are given in Tables II and III.388... 

Triazoline aromatization to triazoles can be achieved by oxidation, isomerization reactions, and elimination of stable molecular fragments, all of which require the presence of a free hydrogen at position 4 and/or 5 of the triazoline ring. The aromatization reaction affords a selective, synthetic route for the preparation of triazoles of definitive structure, inasmuch as azide addition to acetylenes is not regioselective.33... 

An unusual course of thermolysis occurs in 5-amino- and 5-alkoxytri-azolines, which are formed only as intermediates in the reaction of enamines and enol ethers with azides bearing electron-withdrawing groups it involves cleavage of the N-l/N-2 as well as the C-4/C-5 bonds of the triazoline ring to yield diazoalkanes and imines with one fewer carbon than in the triazolines (amidines and imino ethers) (Scheme 144)233.250 272 431-433 in a cycloelimination reaction, the reverse of diazoalkane-imine cycloaddition. The intermediate formation of a diazonium zwitterion is suggested,233,247 but whether the thermolysis occurs in a one- or two-step reaction is not established. 

Triazoline ring cleavage with nitrogen expulsion can be achieved by photolysis or thermolysis and leads to aziridines, imines, or the isomeric enamines.12 In contrast to thermolysis where product mixtures are obtained, photolysis is more selective and aziridine is the major product.27,79,2 2-290... 

Hydroxytriazolines generally yield triazoles by loss of water (Section IV,A,3,b). However, the fused-ring triazolines 110 and 111 when heated lead to amides 112 and 113.260 Formation ofl 13 involves the cleavage of the C-4/C-5 bond of the triazoline ring both amides also result by the action of acid on the respective triazolines. 

The isoindolinotriazolines (Scheme 86) are exceptions when X and/or Y = CN, a mixture of an exocyclic enamine and an isoindolenium methylide is formed via a zwitterionic intermediate, which is proposed to involve a C—N rather than an N—N bond cleavage of the triazoline ring (Scheme 189).324... 

The thermolysis of ethyl azidoformate in excess azobenzene at 115-117°C gives, as the major product, ethyl 2-(phenylazo)carbanilate the proposed reaction mechanism suggests the formation of an azimine (8) (by attack of the nitrene on the azo group) which rearranges to the carbanilate via a bicyclic A3-triazoline ring system,18 apparently formed by a 1,5-electrocyclization19 of 8 (Scheme 4). 

Substitution of three carbon atoms with heteroatoms in the pentadienyl anion leads to the structures shown in Scheme 21 (only vicinal N-substitution is considered). The resulting heterocycle is a triazoline ring. Photochromic molecules 43 containing this structural element have been made (Scheme 21).51,52... 

In the first step, formyl ketone 14a reacts via its enol form 14b with tosyl azide in a 1,3-dipolar cycloaddition yielding intermediate 15. Its triazoline ring resolves into the a-diazo ketone 4 and 7V-formyl tosyl amide. 

The 1,2,4-triazoline ring system can be constructed from reactions of acyclic compounds or from transformation of cyclic structures. In the classical approach to triazoline synthesis, the N—C—N—N skeleton of... 

Azomethinimine dipoles could be noncyclic and not an integral part of a heterocyclic ring system, or of the cyclic type that are more or less integrated into a heterocyclic framework. The cyclic dipoles provide routes for the synthesis of a variety of annulated triazoline ring systems. 

NMR measurements are used for structural as well as conformational analysis of complex tri- and tetracyclic fused triazoline ring systems. The H- and 13C-NMR spectra of angularly condensed triazolobenzothiazine... 

Unlike NMR, UV spectroscopic measurements have been used only to a very limited extent for structure identification purposes. Consequently, relevant data are not available for the evaluation of substituent effects on the triazoline chromophore. However, UV data on certain annulated triazoline ring systems indicate that both the position and intensity of the absorption maximum can be affected by annulation for example, dihy-drotriazolobenzodiazepines 18, Xmax = 350-214 nm (log e = 1.8-3.4) (79JOC2688), dihydrotriazolopyridines 25, = 450—430 nm (log =... 

The X-ray crystal structure of 4-benzamido-l-benzoyl-4,5-dihydro-1,2,4-triazoline (176) (87AX(C)168) shows the triazoline ring to be essentially planar with a maximum deviation from a least-squares plane... 

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